Discrete dosages of pharmaceutical compositions suitable for oral administration are conveniently administered as solid dosage forms, typically tablets. In addition to the therapeutic ingredient or ingredients (commonly referred to as “actives,” “active pharmaceutical ingredients,” or “API”), the tablet comprises pharmaceutically acceptable materials, known as excipients, that are not actives and do not provide a therapeutic effect, but are added to the tablet formulation to confer specific properties not related to the activity of the active.
There are three general methods of preparation of tablets: (1) direct compression; (2) dry granulation; and (3) wet granulation. In direct compression, the powdered material(s) to be included in the tablet (including the active and the excipients) are blended together and compressed directly without intermediate processing, such as granulation. Although direct compression is the most effective and favorable manufacturing process for the production of solid dosage forms, such as tablets, many tablet formulations cannot be processed using direct compression due.
Granulation procedures may be used where poor flow or low bulk density of the direct compression mix precludes tabletting by direct compression. Granulation also improves content uniformity of the active, and reduces dust generation. Dry granulation includes mixing the ingredients, roller compacting or slugging the mix, dry screening or milling to a coarse dry granulate, lubricating, and compressing the lubricated granules. The wet granulation procedure includes mixing some or all of the ingredients and thereafter adding solutions of a binding agent to the mixed powders. The resulting wet mass is screened, dried, lubricated, and compressed into tablets.
In dry granulation, the tablet ingredients are not exposed to moisture, solvents and heat. Thus, it can be used to process moisture, solvent and/or heat sensitive actives. Dry granulation can be carried out by slugging or by roller compaction. Slugging is a double compression process. The material to be tabletted is compressed to a large compressed mass, or “slug,” which is converted to tablets by a second compression process. Because slugging is a slow and uneconomic process, roller compaction has become the method of choice for dry granulation. Roller compaction has all the benefits of a granulation process, such as improved material flow behavior and content uniformity. In addition, roller compaction is high-volume and more economical to operate than wet granulation.
During the roller compaction process, at least a portion of the tablet formulation (the “granulate formulation”) is compacted and densified by two counter-rotating high-pressure rollers, and the resulting material milled to uniform size. The resulting granulate may be subsequently tabletted with or without additional excipients to form tablets. The tablet is formed by pressure acting on the tablet formulation in a die on a tablet press. A tablet press includes a lower punch which fits into a die from the bottom and an upper punch having a corresponding shape and dimension, which enters the die cavity from the top after the tablet formulation fills the die cavity. The tablet is formed by pressure applied to the tablet formulation in the die by the lower and upper punches.
Because of its inherent compactability characteristics, microcrystalline cellulose (MCC) finds widespread use as an excipient in pharmaceutical formulations. Good binding and disintegration properties are also obtained when MCC is used in tablet formulations.
Tablet formation by roller compaction followed by tabletting includes two compaction steps. However, after the first compaction step, the MCC granulate may have insufficient compactability for the second compaction, i.e., tabletting, step. Therefore a need exists for microcrystalline containing binders that can be used to prepare solid dosage forms by processes involving multiple compaction steps such as roller compaction and tabletting, or slugging. The binder must have sufficient compactability for the second compaction step.